Sequential Firing Codes for Time in Rodent Medial Prefrontal Cortex

Abstract

A subset of hippocampal neurons, known as "time cells" fire sequentially for circumscribed periods of time within a delay interval. We investigated whether medial prefrontal cortex (mPFC) also contains time cells and whether their qualitative properties differ from those in the hippocampus and striatum. We studied the firing correlates of neurons in the rodent mPFC during a temporal discrimination task. On each trial, the animals waited for a few seconds in the stem of a T-maze. A subpopulation of units fired in a sequence consistently across trials for a circumscribed period during the delay interval. These sequentially activated time cells showed temporal accuracy that decreased as time passed as measured by both the width of their firing fields and the number of cells that fired at a particular part of the interval. The firing dynamics of the time cells was significantly better explained with the elapse of time than with the animals' position and velocity. The findings observed here in the mPFC are consistent with those previously reported in the hippocampus and striatum, suggesting that the sequentially activated time cells are not specific to these areas, but are part of a common representational motif across regions.

Temporal and spatial context in the mind and brain

“…These predictions resemble the properties of hippocampal “time cells” that fire sequentially during a circumscribed period within a delay period [60, 49]. Consistent with the hypothesis that the compressed representation of the past is accessed in many different forms of memory, time cells are not only observed in the hippocampus [51], but also the entorhinal cortex [52], striatum [54, 61], and medial PFC [53, 62]. Notably, in all of these studies, time cells show a characteristic compression as qualitatively predicted by theory (Fig.…”

“…The theoretical framework in [50] predicts a linear increase. Clockwise from top left, rodent hippocampus (different colors for CA1 vs CA3) [51], rodent medial entorhinal cortex (different colors show grid cells vs non-grid cells [52], medial prefrontal cortex [53], and striatum (different colors are different delay durations) [54]. …”

A neural microcircuit model for a scalable scale‐invariant representation of time

“…Critically, the firing rates of the sequentially activated time cells are scale‐invariant. This provides a possible neural substrate for the scalar timing behavior observed across a wide range of timescales in behavioral tasks, and also approximates the neurophysiological recordings of sequentially activated cells that have been observed across a wide range of regions of the cortex including the hippocampus (MacDonald et al, ; Salz et al, ), PFC (Tiganj et al, ), and striatum (Adler et al, ; Mello et al, ).…”

“…Time cells were observed when an animal is performing delayed match to sample (MacDonald, Lepage, Eden, & Eichenbaum, ), delayed match to category (Tiganj, Cromer, Roy, Miller, & Howard, ), spatial alternation (Salz et al, ), or temporal discrimination tasks (Tiganj, Kim, Jung, & Howard, ). Time cells have been found in various parts of the brain including the hippocampus (MacDonald et al, ; Salz et al, ), prefrontal cortex (PFC) (Bolkan et al, ; Jin, Fujii, & Graybiel, ; Tiganj et al, ) and striatum (Adler et al, ; Akhlaghpour et al, ; Mello, Soares, & Paton, ). A recent study suggests that neurons in the amygdala are sequentially activated during the intertrial interval of a conditioning task (Taub, Stolero, Livneh, Shohat, & Paz, ).…”

Memory integration constructs maps of space, time, and concepts

“…Recent evidence suggests that temporal proximity affects memory integration at a range of timescales, which involve distinct mechanisms [50]. Memory integration at time scales on the order of seconds may be organized by “time cells” in the hippocampus and mPFC, which respond at specific temporal intervals during task performance [51, 52]. Computational modeling suggests that, like place cells, time cells may provide a map for organizing sequences of memories [53].…”